Smoking and tobacco dependence cause myriad diseases and almost half a million deaths in the United States each year, including one-third of all cancer deaths. A new technology, electronic cigarettes (e-cigs), which allow the user to inhale nicotine vapor, has seen rapid adoption in the US. The extant data on e-cig use and its effects are extremely limited at a time when regulatory policies are being considered. The proposed research will provide in-depth, longitudinal data, based on real-time reports, which will address key priorities for the US Food and Drug Administration, including understanding the relations between e-cig use and: 1) nicotine dependence; 2) reductions in conventional cigarette (CC) use; 3) health-related outcomes such as biomarkers of exposure and carcinogens and acute and long-term pulmonary health; and 4) attempts to quit CC use and the success of those attempts. Specifically, we will conduct a 2-year longitudinal cohort study comprising smokers who exclusively smoke CCs (N=150) and dual users of e-cigs and CCs (N=250). We will use state-of- the-art ecological momentary assessments to determine: 1) dynamic patterns of e-cig and CC use and related outcomes (e.g., dependence, withdrawal symptoms, reward value, and CC quit attempts and quitting success); 2) episodic (affective, contextual, social) and stable person-factor (lifestyle factors, demographics) variables that covary meaningfully with e-cig and CC use and related outcomes; and 3) targeted biomarkers of tobacco and carcinogen exposure as well as other health-related outcomes (e.g., pulmonary function). Both within- subjects data (from the dual use group) and intergroup comparisons (dual use vs. exclusive CC use) will allow us to use multiple powerful analytic approaches with this unique and informative dataset. This research will provide essential information to inform regulatory bodies, as well as researchers, clinicians, and tobacco users, about the patterns of real-world e-cig use and how such use is related to CC smoking and the health risks caused by smoking. Thus, this innovative research will collect real-time data that should provide a strong empirical foundation to examine the public health effects of e-cig use during this critical period of emerging policy discussions.